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PMID: 376851 Published · ppublish English Journal Article Review

Inhibition of anion permeability by amphiphilic compounds in human red cell: evidence for an interaction of niflumic acid with the band 3 protein.

The Journal of membrane biology ·Vol. 46 ·No. 2 ·1979-04-20 ·Pages 125-53

Cousin JL, Motais R

Abstract

In human erythrocyte, permeability to the anion is instantaneously, reversibly, and noncompetitively inhibited by the nonsteroidal anti-inflammatory drug, niflumic acid. The active form of this powerful inhibitor (I50 = 6 X 10(-7) M) is the ionic form. We demonstrated that: (i) The binding of niflumic acid to the membrane of unsealed ghosts show one saturable and one linear component over the concentration range studied. The saturable component vanishes when chloride transport is fully inhibited by covalently bound 4-acetamido-4'-isothiocyano stilbene-2,2'-disulfonic acid (SITS). Our estimate of these SITS protectable niflumate binding sites (about 9 x 10(5) per cell) agrees with the number of protein molecules per cell in band 3. These sites are half-saturated with 10(-6) M niflumic acid, a concentration very close to I50. (ii) Niflumic acid inhibits the binding reaction of SITS with anion controlling transport sites. These results indicate that niflumic acid and SITS are mutually exclusive inhibitors, suggesting that niflumic acid interacts with the protein in band 3. Niflumic acid also decreases glucose and ouabain-insensitive sodium permeabilities. However, these effects are produced at a very high concentration of niflumic acid (in millimolar range), suggesting unspecific action, possibly through lipid phase.

MeSH Terms
Anions Binding Sites Biological Transport, Active/drug effects Blood Proteins/metabolism Cell Membrane Permeability/drug effects Chlorides/metabolism Erythrocyte Membrane/drug effects,metabolism Erythrocytes/drug effects Glucose/metabolism Humans In Vitro Techniques Nicotinic Acids/pharmacology Niflumic Acid/metabolism,pharmacology Stilbenes/pharmacology Temperature
Chemicals
Anions Blood Proteins Chlorides Nicotinic Acids Stilbenes Niflumic Acid Glucose
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Cousin J L
Motais R
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Article Info
Journal
The Journal of membrane biology
Abbr.
J Membr Biol
ISSN
0022-2631
DOI
10.1007/BF01961377
Published
1979-04-20
Pages
125-53
Language
English
Region
United States
NLM ID
0211301
Subset
IM
External Links
PubMed source DOI: 10.1007/BF01961377 View journal details
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